Bongo, Welcome!  First of all, let me just say that I fully second all of Jack's remarks.  Smoking, VED, Vitamin E, he is exactly right about all of those.  Above all, smoking will actively promote the process that is causing your problems.  You should be seeking medical help in dealing with that issue.  The faster you can eliminate smoking from the equation, the better off you will be.  However, I would add the following:

1) There are ONLY two oral treatments that have shown any measurable success in treating Peyronies in a research setting.  Those are Pentoxifylline and Acetyl-L-Carnitine.  Thats all.  So those are the two I would focus on.  Since Pentox causes bad side effects for you, Pentox apparently is out.  That leaves ALC.  So, if I were you, I would make ALC a cornerstone.  But remember, any successful treatment of Peyronies is going to be a VERY long term project.

2) Personally, I identify Peyronies with a process known as Glycation.  Glycosylation is a normal process in the body wherein glucose is purposely joined to protein.  Lately researchers have identified a rogue version of this process which fuels fibrosis.  This is known as "Glycation".  One of the few things that Pentoxifylline and ALC have in common is that they are both antagonists of Glycation.  Since there are a quite a few anti-Glycants around, I have been building a supplement stack of anti-Glycants.  Those are serving me well and not only preventing my Peyronies from becoming worse, but I am actually experiencing a very gradual improvement with shrinking plaques and increasing flexibility.  Here is my current list:

Carlson Aloe Vera Soft Gels  - Protein Turnover Agonist
Benfotiamine Inc. Benfotiamine-V  - AGE-Breaker
Jarrow Formulas Pyridoxall with Pyridoxamine  - AGE-Breaker
Jarrow Formulas CarnitAll 600  - Anti-Glycant *Includes ALC*
Now Foods NAC  - Anti-Glycant
Now Foods L-Carnisone  - Anti-Glycant
Natural Factors Mangosteen Super Strength Extract  - Anti-Glycant
Now Foods Pyruvate Extra Strength  - Anti-Glycant

3) Nothing speaks louder than success.  I have really been contemplating a post in the "Improvement" thread by myrddin back in June of last year.  He notes experiencing very substantial improvement and also notes which supplements he had been taking:

Quote from: myrddin on June 18, 2007, 09:03:17 AM
I had my latest checkup recently with my Urologist (Dr. Culley Carson, UNC Chapel Hill) and was able to report some improvement, so I thought I'd share the same info with my friends here too.

I've been on Pentox almost 9 months now, maybe it takes that long for it to kick in or something. (?)

Background:
At 2-3 months of Pentox, my condition (upward curve) continued to worsen slightly, and had developed a slight left-sideward deviation as well.
At 4.5 months of Pentox, my condition had stablilized but not improved.

Now at 8.5 months, I can definitively say that all sideward deviation is gone.  My unit's perfectly centered when erect.  The plaque on the side (where it used to curve left) cannot be felt anymore.  Also, the upward curve is, in my subjective opinion, not as bad.  Visually it does not seem as sharp an angle as I remember it was a few months ago.  Intercourse has been easier lately and my unit does not seem to be as easily bendable, at the point of the curve, while erect.

All of this improvment has just occurred in the past 2-3 months.  It may be just due to the Pentox, but I had also made a few changes in my Oral Supplements at that point in time.  I replaced Arginine with Sann Vasoflow and tried a month on a PPC (Polyenylphosphatidylcholine)/SAMe regimen.  

Now, FWIW, my current oral intake list looks like this:

On empty stomach:
Sann Vasoflow (2 pills per day)
ALC (500 mg 2x/day)

After meal:
Pentox (2 per day)
Now Foods Gamma-E Complex (2 per day)
Jarrow PolyPC (1000mg 2x/day)
RxOmega-3 Factors (1x/day)

Based on this account, I am planning to start taking PolyPC soon along with the other supps I have listed above.  Additionally, like myrddin, I also use the SANN VasoFlow and Now Foods Gamma-E.  But I am convinced that it is the others that are the more active part of the solution.

We wish you the best as you sort through your options.

- George

I have an appointment with Dr. Steven Schlossberg in Norfolk Va.  I understand that he works with Dr. Jordan.  Do any of the members of this forum know anything about this Doc? Thanks.

NIHs office of rare diseases has announced research funding. Peyronies is considered a rare disease covered by this agency. I have considerable experience with federal grants, but need to hook up with a researcher, foundation, physician, etc.

Any contacts that you can give me would be appreciated.

I would start with Tom Lue in SF. Dr Gonzalez-Cadavid (sp?) in LA is also active in research. Talk to them and see what they would like.

Tim

If you are diagnosed with Peyronie's, should you avoid erections / sexual activity, or should you be as active as possible?

I think the watchword is caution.  Erection is good because it brings in oxygenated blood to promote tissue health and healing.  However, you don't want to engage in activity that causes bending or any further damage, especially in the active or inflamatory stage.  So sex/masturbation is fine - just be gentle and careful.

Nemo

DJW
I agree with Nemo. Do not stop having sex and erections. The penis needs fresh blood daily to keep the corpora's healthy.
After Peronies hit me the night time erections slowly went away. I did not pay much attention and ended up loosing 1.25" in length.
Get a good uro. Have a complete Testesterone and Thyroid check. I had the double whammy of Peronies and low Testesterone (T).
I'm lucky because my curve straighten in about 12-18 months. This was 12 years ago and they have better treatments now. I was on Vitamin E 400IU 3 times a day and Pataba. I continued Vitamin E until October 2006 when I had to have heart stents.
If you start to loose erections or become less firm get a VED to help maintain a healthy penis.
Good Luck. There is tons of help on this board.
Jackp

Quote from: Nemo on February 24, 2008, 12:17:49 AM
I think the watchword is caution.  Erection is good because it brings in oxygenated blood to promote tissue health and healing.  However, you don't want to engage in activity that causes bending or any further damage, especially in the active or inflamatory stage.  So sex/masturbation is fine - just be gentle and careful.

Nemo

Thanks for the replies. This may be a stupid question, but is intercourse considered an act that causes bending?

By the way, it great to be able to talk to other people with the same condition. You don't hear much about it in general.

Quote from: jackp on February 24, 2008, 06:02:22 AM
DJW
I agree with Nemo. Do not stop having sex and erections. The penis needs fresh blood daily to keep the corpora's healthy...I'm lucky because my curve straighten in about 12-18 months[/b]. This was 12 years ago and they have better treatments now. I was on Vitamin E 400IU 3 times a day and Pataba.

Jackp,

Do you mean that your curvature resolved itself after 12-18 months with just Vit E and Potaba? Do you consider yourself completely healed?

DJW, in some cases, intercourse is responsible for Peyronie's in the sense that some guys (myself included) had an "accident" during sex during which the girl came down wrong, or you slipped out and "jammed" it against the pubic bone, or any number of sexual accidents which cause trauma or an acute bend to the penis which tears some tissue inside, causing scaring and then bending (classic Peyronie's).  However, some guys get it with no trauma they can recall - it's very mysterious in that sense.  My 71 year old Dad woke up with Peyronie's one morning and he hasn't had sex in years (he's diabetic).  Some feel it may be genetic for some people, a sort of tissue disorder.  

But more directly, no, normal intercourse doesn't cause problems, you just have to be careful of bending, awkward positions that put stress on the penis, or accidents.  Bottom line, be careful and talk to your woman about how you need to be careful, and sex shouldn't be a problem.  For instance, my girlfriend knows that right now (while I think I am in an inflamation stage) there's no girl on top action allowed.  

Good luck,
Nemo

DJW
Yes the curve corrected! Completely Healed -- NO!!!!!
Even though the curve straightened the problem spread to the corpora's. This caused loss of length and ED to the extent that I am now 100% impotent and the only thing that allows me to have sex is a VED with constriction bands.
Yes I tried all the pills, V,C&L. The shots PGE1 (Edex) and trimix. The shots only made things worse. I even tried a drug in Mexico that melts under your tongue (don't remember the name).
It took about 10 years for the ED to become so bad. The last two years been with the VED. I had a failed implant last October because of the scar tissue in the corpora's that caused a puncture of the urethra. Now I am about 3.5 weeks post back surgery and have to wait about another 5 months for a retry with the implant.
Why do I tell you all this? All I recommend is get to a good Uro ASAP. Shrinkage is very sneaky. If you go the VED route ask your Doctor to give you a prescription for one and have the rep fit it for you. Ask OLD MAN for advice on a VED he is the PRO.
I understand that I am one of the lucky ones when it comes to straightening.
Good Luck,
Jackp

Thanks again for the replies, I appreciate it.

DJW:

You asked if having sex (intercourse) with Peyronies Disease would cause bending, etc. Yes and no, safe gentle sex while exhibiting sypmtoms of Peyronies Disease would be all right to do. But, just do not do the woman on top with all the extra hard thrusting and moving about while you are penetrated. Other positions are safe to use, but again use caution and do any action what would put excessive pressure on the penis. Slow, gentle sexual actions can be just as satisfying as the fast violent manuever ones and much safer. A lot of us wish that we had adhered to that many years ago!!!

Old Man.

There has long been concern about Testosterone Replacement Therapy and risks of Prostate cancer.  Of course, that begs the question as to why younger people with normal testosterone levels are not at risk for prostate cancer.  Researchers are now finding answers to that question and those answers should make all of us sit up and take notice.

1)  Researchers have now discovered that Cardiac Peptide Hormones are POWERFUL anti-cancer agents.

2)  Researchers also now know that Cardiac Peptide Hormones are POWERFUL stimulators of testosterone (which explains why testosterone, WHEN STIMULATED BY CPHs, is benign EVEN THOUGH it is NOT when stimulated artificially in the absence of those protective CPHs).  Incidently, this protective effect likely applies to women in connection with estrogen and would explain why older women are at greater risk of estrogen induced cancers than younger women.

3)  Any degree of cardiac impairment is now known to REDUCE levels of Cardiac Peptide Hormones thus driving up not only cardiovascular risk, but also cancer risks.  (An exception is outright heart failure which actually raises levels of Cardiac Peptide Hormones).

4)  Regular exercise has been shown to RAISE levels of Cardiac Peptide Hormones, thus protecting not only the cardiovascular system, but also from cancer on a systemic basis.

5)  Obviously, diet and its impact on maintaining cardiac health and normal levels of CPHs has HUGE importance in avoiding this unfortunate metabolic cascade.

6)  ADDITIONALLY, normal levels of CPHs support normal blood pressure levels IN SPITE of things like elevated levels of sodium in the blood stream which would be expected to elevate BP.

This whole field of study is just huge.  There is ever increasing research supporting the concept that multiple diet and exercise vectors influence vulnerability to and ability to recover from diseases like Peyronies (and worse).  This should indeed be a HUGE wake up call to all of us.

Hello:

I am an attorney representing 3 clients against a urologist for causing Peyronie's disease.  In one case my client is a Board Certified Family Practice physician who was held down on the table against his will for 15 minutes while this urologist tortured him with the cysto.  There were two other people present to hear the screaming.

One of the other clients is my uncle.  He was black and blue in his whole genital area for a month after having a cysto.

I also have a 4th client who is a female - she is now permanently incontinent because of this urologist's refusal to terminate the dilatation when she demanded that it be stopped because of severe pain.

One of this urologist's nurses quit her position because the urologist was hurting so many people.  There are at least 17 other men in this rural area who have also had a similar experience with this urologist.

I have found only one urologist who will testify, but he wants $40,000.00 to do so.  The others all refuse to testify for social reasons (don't want to offend another doc) or that they don't believe Peyronie's can be caused by a cysto.  As noted in my other recent post, there is a substantial amount of recent research showing otherwise. . .

If anyone knows of a urologist who might be willing to spare numerous other men from injury, please let me know.

Robert W. Bright, Esq.
[email protected]

Wow - what a request.

I would suggest going for the assault and battery issue, and throw in the Peyronie's for good measure. All you need to do is show it happened. And that he suffered. You might be able to get someone to testify that the procedure did not go as well as it should have and that he violated standards of care in his behavior. If you could get someone to testify that he HAS Peyronie's, it seems pretty easy to get him to admit that trauma can lead to it. Trauma is the key - it is the lead theory of causation in Peyronies.

I have testified in medical-malpractice cases. I guess it's different for busy surgeons compared to us pediatricians - We agree to work for an hourly wage. Asking for 40 grand up front is disgusting.

Tim

Tim:  Thanks.  Here'e the problem - by law it's malpractice case regardless of whether it's battery or just the cysto.  Between the injured doc and I, we have contacted 15 urologists.  Only had success with the $40,000.00 one - and niether of us is paying that much for an opinion (that urologist was also an attorney, so I guess that explains the ridiculous fee.  LOL).  I raised the insanity of that issue at the West Virginia Supreme Court and they refused to decide that issue.

One thing I am curious about is this:  If I frame it as a battery, I don't know whether or not I need a UROLOGIST to testify to a breach of the standard of care.  I'm reviewing the requirements in the statute.  If not, then I could pretty much use any generalist - especially one who had taken any urology training.

BTW, as a Pediatrician, have you ever done a cystoscopy?  If so, would you be willing/interested in testifying?

Thanks

Rob

I take care of lungs, not penises (peni?). I have looked down windpipes, but not up a penis (think I'd keep it that way too).

It really seems that the fact that urologists make a lot of money makes it less imperative that they take legal cases (which are fairly lucrative).

Going to a doc who is far away makes the most sense - even if you have to network with attorneys across the country. I think that the feeling is this: "Yeah, there is a risk of trauma - we know that going in. Bad things happen sometimes, and that is the way it goes - why go after the poor doc who is just trying to help some poor patient?"

Perhaps if you asked someone who had published literature about cystoscopy to do it  - but the same feelings may apply. Also, getting someone to simply say that there is a risk, and to see if the doc doing the procedure was aware of the risks, and advised about them specifically. That would be a start.

Finally, I have been more willing to take on pediatric lung cases when the attorney knew up front that I may not say something he liked. IOW, I said I will review what you got, but I am not guaranteeing that you will like what I say to you. If I agree that something bad happened, then we can move forward.

If you did that and had an egregious case (it sounds like you do), then you might get your foot in the door, and then go from there.

Tim

From Spain:

Quote from: PubMed[Internet use in patients attending a hospital urology clinic]
[Article in Spanish]

Santos Arrontes D, García González JI, Martín Muñoz MP, Jiménez Jiménez JI, Paniagua Andrés P.

Servicio de Urología, Hospital de Móstoles, Móstoles, Madrid. [email protected]

HYPOTHESIS: The increase in the awareness of computers in the general population and the spread of Internet as a tool for communication and knowledge, allows patients to have greater understanding of their conditions. OBJECTIVE: To evaluate the use of Internet by the population from a health area and the knowledge extracted about their urological conditions. MATERIAL AND METHODS: This prospective study included all patients of age who attended a hospital urology clinic between 1st September and 31st December 2006, in a health area of 200,000 inhabitants. All patients were given a self-administered questionnaire to complete; medical staff did not intervene in filling it out in any case. The study variables were age (under 30, between 30 and 60 and over 60), sex, patient's pathology (only those with at least 5 cases were assessed), educational level (none, primary school qualification, intermediate studies and university studies), presence of a computer at home (yes/no), knowledge of the existence of internet (yes/no), searches performed on urological conditions and influence of these consultations in their relationship with their doctor. The relationship between the use of internet and the different variables was evaluated using the Kruskall-Wallis test. A probability of the null hypothesis less than 0.05 was considered significant. RESULTS: A total of 1,111 questionnaires were received, of which 1,062 were useful for processing. The mean age was 60.98 with a standard error of 15.08. 18.4% were women. The population distribution by level of studies was: 22.2% uneducated, 43.5% with primary education qualification, 27.5% with intermediate educational level and 6.8% university graduates. 58.4% of patients denied having a computer at home, 37.7% do not know what internet is, 76.7% do not have an e-mail address and just 6.7% visit medical pages, although only 1.5% admit having asked their doctor about information received on internet. According to classification by age, patients under 30 have significantly greater knowledge of computers and internet (p<0.001). However, there were no significant differences shown between the age and the fact of asking about information received through internet (p=0.1). The most visited web pages were, in order of the most to least visited: tuotromedico.com, varicocele.com, aecc.es, wikipedia.com, prostatitis.org, ondasalud.com and mapfrecajasalud.com. The most searched for conditions were: chronic prostatitis (25% of patients affected), testicular cancer (20% of patients), varicocele (18.7%), Peyronie's disease or congenital penile curvature (18.1%) and stenosis of the pyeloureteral junction (16.6%). CONCLUSIONS: --The exploitation of the internet as an information tool on the part of patients is very low, due to the characteristics inherent to our population, such as the low level of studies. --Urological web pages should dedicate an extensive part to the most common conditions in the younger population groups, such as varicocele or prostatitis. However, it is logical to expect that these epidemiological patterns will modify with time. --The use of internet and computers in general should be promoted among the different population groups in the health area under study.

PMID: 18314655 [PubMed - in process]

Here is an interesting abstract of a paper outlining current Peyronies treatments and their perceived efficacy:

Quote from: PubMedPharmacological Management of Peyronie's Disease.
Trost LW, Gur S, Hellstrom WJ.

Department of Urology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.

Peyronie's disease is a localised, fibrosing condition of the penis that occurs in up to 9% of men. Although its aetiology has not been elucidated, Peyronie's disease probably results from the presence of a predisposing genetic susceptibility combined with an inciting event, most probably trauma. Following appropriate clinical evaluation, initial treatment consists of a trial of oral and/or intralesional pharmacotherapy. Oral therapies most commonly employed include para-aminobenzoate (Potaba) and tocopherol (vitamin E), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less frequently. Placebo-controlled studies examining these agents have failed to show a consistent beneficial effect on Peyronie's disease, with the exception of para-aminobenzoate, which may decrease plaque size and curvature, and acetyl-L-carnitine, which may reduce erectile pain and inhibit disease progression. Intralesional injection therapy for Peyronie's disease is commonly used as a first-line therapy along with oral medications. The current standard of care involves injection with interferon-alpha-2a or -2b, verapamil or collagenase over 2-week intervals for a period of 5-6 months. Interferon-alpha-2b, in particular, has been documented in a large, multicentre, placebo-controlled study to be significantly more effective than placebo in decreasing penile curvature, plaque size, penile pain and plaque density. However, interferon treatment is also associated with significant adverse effects, including fever and other flu-like symptoms. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids and orgotein. Surgery is considered in patients with Peyronie's disease who have not responded to a trial of conservative medical therapy for 1 year and who are precluded from sexual intercourse. Procedures commonly performed include the Nesbit procedure (or variations of the Nesbit), penile plaque incision/excision with or without grafting, and implantation of a penile prosthesis. Further basic scientific research in Peyronie's disease is likely to identify additional targets for future pharmacotherapy.

PMID: 17352513 [PubMed - indexed for MEDLINE]

Hi,

I found this fascinating article about regeneration of body parts and the potential for humans to do so in the near future (10-15 years). Equally as fascinating  is a discussion about the role fibroblasts play in the healing/scarring process.

I recommend anyone with an interest in these topics check out the article... I am sure I am not doing it justice.

http://www.sciam.com/article.cfm?id=regrowing-human-limbs&print=true

Very interesting article!

Thanks for the link.

Hi Guys.

After my first Uro visit eight months ago I immediately started taking vitamin E, as it was the only thing besides surgery suggested.  Then when I found the PDS web site a few months back, and began my real education, I started taking ALC, and eating better.  Now, in addition to these supplements, and various life changes, I'm doing traction, and the vacume.  

In the event When, (I'm determined to remain optomistic here) I start seeing improvement, and can make an account there of on this topic...which treatment worked?

Playing devils advocate here, but really, how do we know if it was the VED, or the traction, or the oral treatments, injections, etc., etc.?

There's not a lot of "control" going on around here...

AR

This is an interesting article which seems to indicate that vascular plaque "eats" and depletes nitric oxide.  IF the same process takes place in the case of Peyronies, it would seem to explain a lot of things.  Perhaps Arginase is not the ONLY issue concerning NO depletion?

Quote from: HealthDayThe finding, scheduled to be presented this week at the American Chemical Society annual meeting, in New Orleans, centers around the availability of nitric oxide (NO), an important gas within the body that relaxes blood vessel walls and helps prevent atherosclerosis. Certain substances in plaque remove NO and create a toxic substance known as peroxynitrite, which hampers the function of enzymes necessary to the health of blood vessel walls.

Atherosclerosis May Also Harm Vital Organs  Toxic byproduct of plaque formation wreaks havoc on heart, lungs and liver, study suggests

I'm not sure how this could help us.  Any comments appreciated.

Latent TGF- and its intricate activation process

TGF- is synthesized as a prohormone that is cleaved in the secretory pathway into an amino-terminal propeptide and a carboxy-terminal fragment that constitutes the mature growth factor (Fig. 4). Unlike most other hormones, the mature TGF- remains noncovalently associated with its propeptide after secretion (for review, see Roberts and Sporn 1990). Mature TGF- in this complex is not recognized by the signaling receptors; hence, the term latency-associated protein (LAP) designates the TGF- propeptide. A family of large secretory glycoproteins known as latent TGF--binding proteins (LTBPs) covalently bind to LAP via disulfide bonds. LTBPs are not required for maintenance of TGF- latency but may instead facilitate the secretion, storage, or activation of the TGF--LAP complex.

The physiological activation process of latent TGF- is currently understood only in part, but it seems clear that this is a multistep process. Many different components including the plasminogen activation cascade, thrombospondin, and the mannose 6-phosphate receptor have been suggested to be involved in this process (Taipale et al. 1994; Nunes et al. 1997; Rifkin et al. 1997), but recent genetic evidence points at thrombospondin-1 (TSP-1) and the cell adhesion receptor v6 integrin as important participants in this process in vivo. TSP-1, a large homotrimeric protein secreted by many cell types, can activate latent TGF- in vitro through a conformational modification of LAP and appears to be responsible for a significant proportion of the activation of TGF-1 in vivo (Crawford et al. 1998). TGF-1 null mice phenocopy TSP-1 null mice, and systemic treatment with a peptide that blocks TGF-1 activation by TSP-1 causes lung and pancreas alterations similar to those of TGF-1 null animals. A TSP-1 peptide that activates latent TGF-1 reverses these lung and pancreatic abnormalities. In separate studies, the TGF-1-LAP complex has been shown to be a ligand for the integrin v6. v6-expressing cells may induce spatially restricted activation of TGF-1, providing an explanation for the propensity to inflammation in mice lacking this integrin (Munger et al. 1999). A different type of protease, matrix metalloproteinase-2 and -9, which are implicated in tumor invasion and angiogenesis as cell surface-bound proteases, have also been shown to activate latent TGF- (Yu and Stamenkovic 2000).

Activin control by Follistatin

Activin was originally identified as an inducer of follicle-stimulating hormone (FSH) from the pituitary and has a central role in the regulation of the reproductive axis (Gaddy-Kurten et al. 1995). Follistatin is a soluble secreted glycoprotein that suppresses the release of FSH by binding to Activin and inhibiting its interaction with Activin receptors (de Winter et al. 1996). Follistatin can also bind to BMPs, with similar effects (Iemura et al. 1998) and has been shown to induce neural tissue in Xenopus embryonic explants, probably by blocking BMP activity (Hemmati-Brivanlou et al. 1994). As many of the other TGF- family-binding proteins discussed below, Follistatin contains cysteine-rich modules of a type also found in osteonectin, agrin, and other extracellular matrix glycoproteins. These modules may constitute growth factor-binding regions (Fig. 4).

The importance of Follistatin in modulating Activin activity is evident in follistatin-deficient mice, which exhibit abnormal whisker and tooth development and hard-palate defects (Matzuk et al. 1995b). Defects in development of these organs were also observed in Activin A-deficient mice (Matzuk et al. 1995a). follistatin-deficient mice also have defects that are not observed in Activin mutant mice, consistent with a role for Follistatin in regulating other factors. Follistatin is produced and localized to prostate tissue from men with high grade cancer, where it has been proposed to bind to autocrine Activin and inhibit its antiproliferative activity (McPherson et al. 1999).

http://www.caspases.org/showcitationlist.php?chem=Transforming%20Growth%20Factor%20beta

I'm not sure where else to post this.....    Is there any area on this forum where you post your "own" situation and condition? I see in many of the threads requests for "tell us about your condition". I didn't know if there was a particular part of the forum to do this. I'm happy to share my experience, but sounds like mine may be similar to many of you.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=370713

The suppression of collagen production by increasing the cyclic (c) AMP content of cultured cells was examined vis-à-vis the β-adrenergic system. Cultured human fetal lung fibroblasts incubated for 6 h with the β-agonists isoproterenol or epinephrine produced ~30% less collagen per cell than in the absence of the hormones. To demonstrate that the β-agonists were operating by their interaction with the β-receptor to stimulate adenylate cyclase to increase the intracellular content of cAMP, d- and l-isoproterenol were incubated separately with the cultured cells. Only l-isoproterenol increased intracellular cAMP and decreased collagen production. While 20 nM l-isoproterenol was effective, the d-isomer was ineffective even at 2μM. An increase in cAMP from 40 to 73 pmol/mg protein was effective in suppressing collagen production; increasing the cAMP content to much higher levels had little additional effect on collagen production. 3-Isobutyl-1-methylxanthine, an analog of theophylline that inhibits phosphodiesterase, potentiated the effect of isoproterenol in suppressing collagen production. Further support for the concept that isoproterenol suppressed collagen production by acting through the β-receptor was provided by the finding that only the l-isomer of propranolol, a β-blocker, was effective in blocking both the increase in intracellular cAMP and the suppression of collagen production caused by isoproterenol. These results demonstrate that collagen production in human fibroblasts can be regulated by the β-adrenergic system and indicate that when the cAMP content is increased beyond a threshold value, collagen production is suppressed. Since collagen production is sensitive to the small changes of cAMP content of cells brought about by β-stimulation in cultured cells, the results point to a possibly important mechanism for the regulation of collagen production in the body.

see link at top for full published report

 Wednesday, April 16, 7:00 p.m EST Live with Dr. Culley Carson, peyronies expert
« Reply #450 on: Yesterday at 10:39:41 PM » Quote Modify Remove  

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http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20080413005027&newsLang=en

Wednesday April 16, 2008

World-Renowned Peyronie's Disease Specialist, Dr. Culley Carson to Discuss the Signs, Symptoms and Latest Treatment Options for Peyronie's Disease in Online Forum at Menshealthpd.com
Physicians and Patients Encouraged to Join Peyronie's Disease Live Online Chat

BLOOMINGTON, Ind.--(BUSINESS WIRE)--Physicians and patients around the world are invited to a live, online chat event entitled, "Early Stage Treatment of Peyronie's Disease: Options, Expectations and Likely Outcomes" at www.MensHealthPD.com on Wednesday, April 16 at 7:00 p.m. EST led by Dr. Culley Carson, an expert in the treatment of Peyronie's. Recent demographic surveys have reported that Peyronie's disease, also known as penile curvature, can be found in up to nine percent of men between the ages of 40 and 70.1

During the session, men and their partners as well as physicians can ask Dr. Carson specific questions surrounding the signs, symptoms and progression of Peyronie's disease. Dr. Carson is expected to also highlight the common options for treatment and their potential outcomes. People who wish to participate in the chat are encouraged to post questions in advance at www.MensHealthPD.com.

What:
   Live Chat: "Early Stage Treatment of Peyronie's Disease: Options, Expectations and Likely Outcomes."  
Who:
 Dr. Culley Carson, Professor and Chief, Division of Urology, University of North Carolina School of Medicine, Chapel Hill  
Where:
 www.MensHealthPD.com

When:
 Wednesday, April 16 at 7:00 p.m. EST (4:00 p.m. PST, 12:00 p.m. GMT)  

Dr. Carson is the Rhodes Distinguished Professor of Urology and Chief of Urology at the University of North Carolina Hospital, Chapel Hill, as well as Associate Chairman of the Department of Surgery at North Carolina School of Medicine, Chapel Hill. Previously, he served as a Director of the Duke Male Sexual Dysfunction Clinic, and is the Consulting Urologist at several North Carolina hospitals. He has published more than 200 peer review articles and eight textbooks.

"I am excited to lead the live discussion on MensHealthPD.com. The site provides a welcoming community and a unique outlet for both patients and physicians to share their experiences with Peyronie's disease," said Dr. Carson. "For patients, conditions such as erectile dysfunction and Peyronie's can be embarrassing and uncomfortable subjects to discuss. The live chat is a perfect opportunity for them to become better educated on this medical condition and learn about the treatment options available in a discreet environment. Physicians may also gain a better understanding of the questions and thoughts that patients and partners have about the disease."

Launched in February 2008, www.MensHealthPD.com, is owned and maintained by Cook Medical and is designed to provide the latest information on Peyronie's disease. The interactive site offers medical professionals, patients and their partners public and physician forums for discussing Peyronie's disease, posting questions and sharing personal experiences about the condition.

About Peyronie's Disease:

The disease is linked to erectile dysfunction in 20 to 40 percent of the sufferers and is characterized by the formation of a plague or hardened scar tissue beneath the skin of a man's penis. The scarring is non-cancerous and may lead to a painful erection and curvature of the penis during erection.

The modulation of apoptosis by cyclic AMP involves Akt and epidermal growth factor receptor.
http://www.ncbi.nlm.nih.gov/pubmed/15833279?dopt=Abstract
Zhou B, Li F, Chen H, Song J.

Laboratory of molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 32 Yue-Yang Road, Shanghai 200031, PR China.

Adenosine 3',5'-cyclic monophosphate (cAMP) and transforming growth factor-beta are important regulators of many biological processes. In this study we investigated the effect and its potential mechanism of cAMP on transforming growth factor-beta1- and serum deprivation-induced apoptosis in Mv1Lu cells. Transforming growth factor-beta1 treatment or serum deprivation induces apoptotic response in Mv1Lu cells. Forskolin, a cAMP-elevating agent, or 8-Bromo-cAMP (8-B-cAMP), a cell permeable cAMP analogue, inhibited the cell proliferation and markedly enhanced apoptosis induced by transforming growth factor-beta1, but completely suppressed serum deprivation-induced apoptosis. Furthermore, forskolin decreased the Akt phosphorylation, and the inhibition of phosphatidylinositol-3 kinase by LY294002 sensitized Mv1Lu cells to transforming growth factor-beta1-induced apoptosis. In addition, forskolin treatment induced tyrosine phosphorylation of epidermal growth factor receptor. Inhibition of epidermal growth factor receptor by specific inhibitor PD153035 blocked the cAMP-mediated suppression of serum deprivation-induced apoptosis. The results indicate that cAMP exerts its opposite effects in transforming growth factor-beta1- and serum deprivation-induced apoptosis via a mechanism involving the modulation of signaling components of phosphatidylinositol-3-kinase/Akt and epidermal growth factor receptor in Mv1Lu cells.

Is this paper saying that cAMP can slow TGF Beta?

jxyz

Quote from: lwillisjr on April 14, 2008, 10:32:06 PM
I'm not sure where else to post this.....    Is there any area on this forum where you post your "own" situation and condition? I see in many of the threads requests for "tell us about your condition". I didn't know if there was a particular part of the forum to do this. I'm happy to share my experience, but sounds like mine may be similar to many of you.

   Yes there is a place to tell your story. Use this thread: Our Histories - Meet the Forum Members, Read our Stories. You can post your story there one time, then you can go back and modify it as your story develops.

Guys, I think you need to think carefully on this Collagen issue.  The problem is NOT over production of Collagen.  The problem is the accumulation of DEFECTIVE Collagen.  What we want to accomplish here is NOT to stop Collagen production.  What we want to do rather is to get rid of the DEFECTIVE Collagen and replace it with normal Collagen and that is going to take, if anything, an increase in Collagen production.  AND, of course, we need to stop the new Collagen from going bad.  - George

Quote from: jxyz on April 16, 2008, 12:15:11 PM
The modulation of apoptosis by cyclic AMP involves Akt and epidermal growth factor receptor.
http://www.ncbi.nlm.nih.gov/pubmed/15833279?dopt=Abstract
Zhou B, Li F, Chen H, Song J.

Laboratory of molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 32 Yue-Yang Road, Shanghai 200031, PR China.

Adenosine 3',5'-cyclic monophosphate (cAMP) and transforming growth factor-beta are important regulators of many biological processes. In this study we investigated the effect and its potential mechanism of cAMP on transforming growth factor-beta1- and serum deprivation-induced apoptosis in Mv1Lu cells. Transforming growth factor-beta1 treatment or serum deprivation induces apoptotic response in Mv1Lu cells. Forskolin, a cAMP-elevating agent, or 8-Bromo-cAMP (8-B-cAMP), a cell permeable cAMP analogue, inhibited the cell proliferation and markedly enhanced apoptosis induced by transforming growth factor-beta1, but completely suppressed serum deprivation-induced apoptosis. Furthermore, forskolin decreased the Akt phosphorylation, and the inhibition of phosphatidylinositol-3 kinase by LY294002 sensitized Mv1Lu cells to transforming growth factor-beta1-induced apoptosis. In addition, forskolin treatment induced tyrosine phosphorylation of epidermal growth factor receptor. Inhibition of epidermal growth factor receptor by specific inhibitor PD153035 blocked the cAMP-mediated suppression of serum deprivation-induced apoptosis. The results indicate that cAMP exerts its opposite effects in transforming growth factor-beta1- and serum deprivation-induced apoptosis via a mechanism involving the modulation of signaling components of phosphatidylinositol-3-kinase/Akt and epidermal growth factor receptor in Mv1Lu cells.

Is this paper saying that cAMP can slow TGF Beta?

jxyz

Can someone comment on this post.  I believe this to be important information.

Quote from: George999 on August 12, 2007, 06:48:03 PM
I just ran across the following information on elastin.

1)  While elastin production in the body declines precipitously at puberty, it does not cease altogether.

2)  Elastin is important because it adds elasticity to tissue.  One of the effects of Peyronies is to reduce and/or eliminate the amount of elastin in affected tissues.

3) The biological switch for elastin production is cAMP/cGMP ratio.  Increase in cAMP shuts down elastin production (bad).  Increase in cGMP ramps up elastin production (good).

4) Both Icariin (Horny Goat Weed) and Viagra increase cGMP which is good news in terms of elastin.

5) Forskolin increases cAMP levels which means that forskolin with all of its potential benefits may not be good for elastin production.

6) Since reducing levels of cAMP can lead to increased inflammation, this is probably not a solution, rather the target would need to be increasing cGMP levels IN PROPORTION to cAMP levels.

- George

PS - This post has been modified by me due to an error in my initial post.  Icariin actually increases cAMP and decreases cGMP selectively in cancer cells meaning that it may have benefits in fighting cancer.  I originally misinterpreted this as indicating that icariin might be bad for elastin production.

George, if I understand your post correctly you are saying "cAMP increase is bad."  

According to this abstract Pentox increases cAMP.  In essence you are saying Pentox is bad.  Or the abstract is wrong.  What's up?

Here is the abstract:

"Inducible nitric oxide synthase (iNOS) is expressed in both the fibrotic plaque of Peyronie's disease (Peyronies Disease) in the human, and in the Peyronies Disease-like plaque elicited by injection of TGFβ1 into the penile tunica albuginea (TA) of the rat. Long-term inhibition of iNOS activity, presumably by blocking nitric oxide (NO)- and cGMP-mediated effects triggered by iNOS expression, exacerbates tissue fibrosis through an increase in: (a) collagen synthesis, (b) levels of reactive oxygen species (ROS), and (c) the differentiation of fibroblasts into myofibroblasts. We have now investigated whether: (a) phosphodiesterase (PDE) isoforms, that regulate the interplay of cGMP and cAMP pathways, are expressed in both the human and rat TA; and (b) -arginine, that stimulates NOS activity and hence NO synthesis, and PDE inhibitors, that increase the levels of cGMP and/or cAMP, can inhibit collagen synthesis and induce fibroblast/myofibroblast apoptosis, thus acting as antifibrotic agents. We have found by immunohistochemistry, RT/PCR, and Western blot that PDE5A-3 and PDE4A, B, and D variants are indeed expressed in human and rat normal TA and Peyronies Disease plaque tissue, as well as in their respective fibroblast cultures. As expected, in the Peyronies Disease fibroblast cultures, pentoxifylline (non-specific cAMP-PDE inhibitor) increased cAMP levels without affecting cGMP levels, whereas sildenafil (PDE5A inhibitor) raised cGMP levels. Both agents and -arginine reduced the expression of collagen I (but not collagen III) and the myofibroblast marker, α-smooth muscle actin, as determined by immunocytochemistry and quantitative image analysis. These effects were mimicked by incubation with 8-Br-cGMP, which in addition increased apoptosis, as measured by TUNEL. When -arginine (2.25 g/kg/day), pentoxifylline (10 mg/kg/day), or sildenafil (10 mg/kg/day) was given individually in the drinking water for 45 days to rats with a Peyronies Disease-like plaque induced by TGF β1, each treatment resulted in a 80–95% reduction in both plaque size and in the collagen/fibroblast ratio, as determined by Masson trichrome staining. Both sildenafil and pentoxiphylline stimulated fibroblast apoptosis within the TA. Our results support the hypothesis that the increase in NO and/or cGMP/cAMP levels by long-term administration of nitrergic agents or inhibitors of PDE, may be effective in reversing the fibrosis of Peyronies Disease, and more speculatively, other fibrotic conditions."

What got my attention, and which goes to the heart of what many of us dream of, was addressed in their discussion of the results:

"In summary, we propose that pharmacological interventions aimed at elevating NO, cGMP, or PKG levels, and possibly cAMP, in the penis are potentially useful for the treatment of Peyronies Disease, and more speculatively, for other fibrotic conditions. This work has not addressed the question on whether this intervention would induce regression of an already well-formed plaque, but comparison of multiple gene expression profiles in human Peyronies Disease and the related Dupuytren's disease suggests that both conditions are in a dynamic cell and protein turnover involving replication, differentiation, apoptosis, and collagen and extracellular matrix synthesis and breakdown [8, 9 and 10]. Therefore, modulation of any of these processes may eventually involute the plaque, as has been observed in generalized fibrotic conditions [68 and 69]."

FYI, those last two references are:
68. H.S. Lee, G.T. Huang, L.H. Miau, L.L. Chiou, C.H. Chen and J.C. Sheu, Expression of matrix metalloproteinases in spontaneous regression of liver fibrosis. Hepatogastroenterology 48 (2001), pp. 1114–1117.

69. T. Lai, J.T. Fallon, J. Liu, J. Mangion, L. Gillam, D. Waters and C. Chen, Reversibility and pathohistological basis of left ventricular remodeling in hibernating myocardium. Cardiovasc. Pathol. 9 (2000), pp. 323–335.

One final note for those who grow impatient with a lack of obvious results: The single case report on pentox leading to improvement (written by Dr Liu) showed improvement in a man with long standing lesions after TWO YEARS of treatment. Patience is a virtue...

jxyz,  I think the answer to your question goes something like this.  Life is, in many ways, a trade off.  Most things that are beneficial also have a "dark side".  In the case of Pentox, it provides known anti-fibrotic benefits.  While doing this, it may negatively affect elastin turnover.  Thats a tradeoff.  But until anything better than Pentox is found, it may be a worthwhile tradeoff.  In the case of Forskolin, it has shown no evidence thus far of being beneficial in the case of Peyronies.  Thus, it would probably NOT be worth the trade off.  However, even Forskolin was worth the tradeoff for me.  I was having very difficult to treat urinary tract infections.  Forskolin helped greatly in resolving that problem through its effect as a smooth muscle relaxant.  Through the many months I was taking it, whatever negative effect it had on my Peyronies was imperceptible.  However, its benefit in terms of UTI's was VERY perceptible.  Now my UTI problem is solved and I am off the Forskolin, but if the UTI problem recurred, I would be back on the Forskolin without batting an eyelash.  So the lesson is that it is good and important to know these details, but then one has to step back and weight the risk to benefit equation as carefully as possible.  It is all to easy to be overly cautious and sustain a net loss as a result.  Bottom line:  Pentox is a good drug for Peyronies and I still highly recommend it.  - George

I never read this thread, so I hope there's a better place a mod could move this to. I just want to say, there's a good salon article on peyronie's. Here is a link to some of the response letters.

I found particularly interesting that one reader said sex every other day helped him. This seems to go along with my experience perhaps.

http://letters.salon.com/mwt/feature/2007/09/28/crooked_penis/view/index3.html?show=all

Sweeper:

Welcome to the Peyronies Disease forum. Sorry to hear that you have joined the Peyronies Disease club though. Your history sounds just like a lot of us on here. Some sort of injury caused this horrible mess to start.

Word of advice for you though. Don't wait any longer to seek good professional help. Self medicating in this case does not always work well. Getting some treatment started early on in Peyronies is the best approach. When seeing a urologist try your best to get one that has experience in treating Peyronies. There are not a lot of them around, but some are very good at what they do.

Read everything you can on this forum. There is more good information on Peyronies Disease here than there is in the uro field.  We have been through the fire and know works and what does not. Most uros do not have this background. So, bottom line, do your homework and you will be years ahead in helping yourself.

All of us here are in the same boat and we help each other. Just ask any and all questions you might have and there will be someone who can help you.

Best to you, Old Man

THE USER "shhww3" IS USER IS BANNED FOR SPAMMING OUR FORUM

Hawk

Looking for ways to cut back on systemic inflammation?  Here are some tips:

DrWeil.com

Quote from: DrWeil.comAGEs give food appetizing tastes and smells but in the body have been linked to inflammation, insulin resistance, diabetes, vascular and kidney disease and Alzheimer's disease. ... The blood tests showed that people age 65 and older had AGE levels 35 percent higher than those in the younger group, and that the greater the consumption of foods high in AGEs, the higher the levels of CRP and other markers of inflammation. They also found that in some cases, AGEs levels were very high in some members of the younger group. Here, too, the higher the levels of AGEs, the higher the CRP and other inflammatory markers.

I think I get what just happened...

Schwing posted a troll post here and it was modified by Hawk to read that he was banned - I could not figure out why it was posted with his shings name to it.

Tim

I was wondering if the type of shrinkage that happens to people who have Peyronies Disease is the same as other types of shrinkage?  I do not have detectable fibrosis anywhere, but I have lost 3 cm at least due to an injury I guess.  It is almost as if the tissues have been remodeled or restructured or something.

I was just wondering whether anyone had any idea whether the ved therapy would work for this particular type of shrinkage, or is there no difference b/w the shrinkage caused by classic Peyronies Disease and other types?  Thanks.

josethby:

Based on my experience with VED therapy for ED as well as Peyronies Disease, I would say that VED therapy would help with any type of shrinkage. It should help whether or not the shrinkage is caused by Peyronies Disease symptoms or by just sexual inactivity. There is an old saw that says: "If you don use it, you lose it." and I have found that to be true in my personal case. After prostate cancer surgery that left me totally impotent, I had no sexual activity for several months and my penis shrunk to almost nothing is size. So my conclusin is that the VED therapy can and will help with most cases, etc.

Old Man

Fred, I would recommend that you read this article:

http://www.asiaandro.com/1008-682X/10/79.htm

It has some good information in it that you might find useful.  

crazybrab:

Thanks for your post and welcome to the forum!

I was curious, why do you think the specialists told you VED is a "no go area" and instead wanted to try the shockwave therapy?

Also, when you say it had straightened out again after massaging, do you roughly know what sort of angle improvement that translated into?

wayne999,

Straightening of about 40 degrees, down to about 5-10 degrees. I attribute this purely to regular massaging with cocoa butter/vit E, and subsequent stretching of 'softened' tissue during masturbatory sessions.

Shockwave therapy is one of the few peyronies treatments offered by the National Health Service in the UK, so I might just as well give it a try. As it has been endorsed by the NICE (National Institute for Clinical Excellence) here in the UK, previous clinical trials would have produced statistically positive and significant results. Hopefully, it will help me too!

BTW, great forum, great people, keep up the good work everyone!

BENT 70 - pentox's equivalent is called TRENTAL 400 and you can get it in Aust - which Uro are you going to as mine in Oz prescribed trental to me..

Hello everybody..

I have got one simple question....I had really been into swimming before the onset of my fibrosis...and since that, I avoid it a little bit, because I am not sure if it's good for the condition. Now, because of my back and neck problems and also as a regular excersie, I would like to start to swim again. So what do you think about a cold water (in a poll) regarding this condition ?   Thanks for replies.
R3

IMHO...   you shouldn't let this disease slow you down. I don't think the "cold water" during your swimming would have any effect.

Hi, This is my first post; I am 44yr old in the U.K. and have this curve to the left between 30-40 degrees for as long as I can remember (its almost a banana shape).  I saw a Uro who offered surgery about 5 yrs ago. There is no pain during sex ( just to say lately after sex in the middle of night I find myself waking up with an erection which can be quite painful and quite rigid!!). 6 months ago I had blood in my sperm. This was due to uncomfortable sex position so I went to see a different Uro as I still wasn't sure if it was Peyronies. Upon checking he found no bumps or lumps and put it down to Cong. curve. However the curve did increase by about 5-10 degrees after the sperm in blood incident. Again I was told by this Uro the curve wasnt bad enough to go for Surgery but could have it done if I chose to. I am left with worry if this could get worse and what options are there other than Surgery? Is Pentox or Traction any good? The Uro in the U.K. hasn't heard of Pentox before and says the only option is surgery. Thanks.

godzilla uk
Before you opt for surgery try the VED. If it is peyronies it will help if cong. may not but worth the try.  Go to the VED section and chat with Old Man. I did and regained almost half of shrinkage due to peyronies before implant surgery.
I had blood in my sperm a while back. Went to the doctor he did an exam and said everything was OK. Said that it happens sometimes especially if we put a lot of pressure on the prostate like on a bike. (Stay off Bikes without the proper support.)
I was just wondering if your curve is cong. why did he want to operate?
Jackp

Godzilla U.K.
Typical treatments for congenital curve are either traction or the VED.  It is my understanding that congential curvature is more difficult to treat, but is worth trying. I don't know of any drugs that will help congential curve since there isn't any plaque or fibrous tissue to try to attack. So traction or VED may be your only options.

Surgery can be an option in cases of extreme congential curvature. But from what you describe you have a "mild" curve and no problems with intercourse. I would not recommend the surgery if you are not having any other problems.